The melatonin-cytokine connection in rheumatoid arthritis
The melatonin-cytokine connection in rheumatoid arthritis
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DOI：
10.1136/ard.2005.038588
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发表时间：
2005-08-01
影响因子：
27.4
通讯作者：
Maestroni, GJM
中科院分区：
文献类型：
--
作者：
Cutolo, M;Maestroni, GJM
松果体提取物中的一种物质，能使两栖动物和鱼类的皮肤黑素细胞变白，于1958年被分离出来，称为褪黑素(MLT，N-乙酰-5-甲氧基色胺)。1在白天和夜间活动的物种中，夜间缺乏光刺激MLT的生物合成。来自视网膜的电信号到达视交叉上核，而视交叉上核又通过室旁核将输入信号发送到脊髓，然后到达颈上神经节。纤维终止于松果体细胞。2无光可导致松果体细胞去甲肾上腺素释放增加，并激活a1和b肾上腺素能受体。这会触发一系列细胞内反应，导致N-乙酰转移酶(EC 2.3)的激活。1.87)和羟基吲哚-O-甲基转移酶(EC 2.1.1.4)，将5-羟色胺转化为MLT。2MLT的昼夜释放对机体内环境有深远的影响，具有多种生理效应。MLT的主要功能似乎是使生物体在光周期中同步，它可能在生殖、新陈代谢、季节性、体温调节和免疫中发挥作用。MELATONIN和人类免疫系统动物研究表明，MLT与抗原激活的T辅助细胞(Th)上的特定受体结合导致细胞因子产生和免疫功能上调。3总的来说，MLT的免疫增强作用似乎仅限于T依赖抗原，在免疫抑制的情况下最为明显。例如，MLT可以完全对抗应激或糖皮质激素治疗引起的胸腺退化和免疫抑制，4或恢复软组织创伤和失血性休克后抑制的免疫功能。5 MLT还可以挽救用癌症化疗化合物治疗的小鼠的造血功能。6.
Asubstance from pineal gland extracts, which lightens the skin melanocytes of amphibians and fishes, was isolated in 1958 and called melatonin (MLT, N-acetyl-5-methoxytryptamine). 1 In both diurnal and nocturnal species, the absence of light at night stimulates MLT biosynthesis. Electrical signals originating from the retina reach the suprachiasmatic nuclei which, in turn, send inputs via the paraventricular nuclei to the spinal cord and then to the superior cervical ganglia. The fibres terminate at the pinealocytes. 2 Absence of light results in increased norepinephrine release and activation of a1 and b-adrenergic receptors on the pinealocytes. This triggers a series of intracellular responses, resulting in activation of the enzymes N-acetyltransferase (EC 2.3. 1.87) and hydroxyindole-O-methyl transferase (EC 2.1. 1.4), which convert serotonin into MLT. 2 The circadian nocturnal release of MLT has a profound influence on the internal environment of the organism, with diverse physiological effects. The main function of MLT seems to be that of synchronising the organism in the photoperiod and it may have a role in reproduction, metabolism, seasonality, thermoregulation, and immunity.MELATONIN AND THE HUMAN IMMUNE SYSTEM Animal studies have shown that binding of MLT to specific receptors in antigen activated T helper (Th) cells results in an up regulation of cytokine production and immune function. 3 In general, the immunoenhancing action of MLT seems restricted to T dependent antigens and to be most pronounced in immunodepressed situations. For example, MLT may completely counteract thymus involution and the immunological depression induced by stress or glucocorticoid treatment, 4 or restore depressed immunological functions after soft tissue trauma and haemorrhagic shock. 5 MLT may also rescue haematopoiesis in mice treated with cancer chemotherapeutic compounds. 6